DESCRIPTION: The application proposes independent investigator support for a candidate who has been involved in retrovirus research since 1986 and has participated in a number of original and significant studies on the identification of lentivirus target cells, effects of opportunistic infections on immunodeficiency virus pathogenesis, and the role of cytokines in immunodeficiency virus pathogenesis. The objective of this application is to provide salary support, over five years, to reduce the clinical component of the candidates current tenure-track appointment, thus allowing development of his research program and career. The increased time dedicated to research would also allow development of new collaborations. The candidate is in a supportive environment with several central equipment laboratories and service centers. The candidates research focus concerns the role of cytokines in the immunopathogenesis of lentivirus infections and immunomodulatory therapeutic and vaccination strategies to treat or prevent lentivirus infection. a. Candidate: Dr. Gregg Dean received his D.V.M. degree in 1988 and his Ph.D. degree in 1991 both from Colorado State University, Ft. Collins. He then trained as a Post Doctoral Fellow at the University of California, Davis, until 1994, where he then served as Faculty Research Virologist, until 1996. Later that year, he was appointed to his current position of Assistant Professor at the College of Veterinary Medicine, Department of Microbiology, Parasitology, and Pathology at North Carolina State University (NCSU). b. Career Development Plan: Plans are presented to extend the candidate's research program by expanding his technical staff and number of graduate students, to maintain a well funded research program, to train research scientists, and to pursue funding for remodeling of the laboratory animal facilities allowing the establishment of a specific-pathogen-free cat colony at NCSU. c. Research Plan: The core research project (a 5-year R29 funded 7/11/97) consists of three specific aims. First, to comprehensively evaluate cytokine mRNA and protein production within multiple lymphoid compartments of Fly-infected cats, determine phenotype of cytokine expressing cells, and localize cytokine production defects. Second, to determine the significance of IL4, IL10, IL12, TNF-a and IFN-gamma in the immunopathogenesis of FIV. Third, to evaluate L. monocytogenes as a biological vaccination vector and determine the correlates of successful or unsuccessful immunity. The candidate is addressing three additional specific aims through collaborative studies. Fourth, to determine the effect of simian immunodeficiency virus (SIV) infection on cytokine mRNA and protein production in tissues of infant macaques treated and not treated with PMPA. Fifth, to determine cytokine mRNA and protein expression in the thymus of pathogen-free and Fly-infected cats. Sixth, to determine the effect of treatment with insulin-like growth factor-1 on cytokine expression in the thymus and other lymphoid organs in pathogen-free and Fly-infected cats. d. Environment and Institutional Commitment: NCSU has provided the candidate with a private office, 300 sq. ft. of laboratory space, startup funds, access to the central equipment laboratory, and three years of support for a technical assistant.